title: Post-ischemic administration of progesterone reduces caspase-3 activation and DNA fragmentation in the hippocampus following global cerebral ischemia.
abstract: Delayed death of hippocampal CA1 pyramidal neurons following global cerebral ischemia/reperfusion may be mediated, in part, by caspase-3 activation resulting in DNA fragmentation. Progesterone (P4) is known to exert neuroprotective effects in several models of brain injury. This study was designed to assess the effect of P4 on caspase-3 levels and activation, and DNA fragmentation in the hippocampus following global cerebral ischemia/reperfusion. Adult male Sprague-Dawley rats were subjected to global ischemia by the four-vessel occlusion model. P4 (8 mg/kg), or its vehicle were administered i.v. at 15 min, 2, 6, 24, 48 and 70 h of reperfusion. Remaining pyramidal neurons were assesed by the Nissl staining technique, caspase-3 levels and activation by immunohistochemistry and an in situ activity assay, and DNA fragmentation by the TUNEL method. Post-ischemic progesterone treatment significantly reduced the ischemia/reperfusion-induced increase in caspase-3 levels and activation at 72 h, and DNA fragmentation and CA1 neuronal loss at 7 days. Present results suggest the reduction of caspase-3 levels/activation, and DNA fragmentation, as a part of the neuroprotective effects of progesterone against global cerebral ischemia/reperfusion injury.
authors.affiliation: Unidad de Investigación Médica en Farmacología, CMN Siglo XXI, IMSS, México, DF, México.
authors.forename: Claudia
authors.initials: C
authors.lastname: Espinosa-García
authors.forename: Rosa María
authors.initials: RM
authors.lastname: Vigueras-Villaseñor
authors.forename: Julio César
authors.initials: JC
authors.lastname: Rojas-Castañeda
authors.forename: Alejandra
authors.initials: A
authors.lastname: Aguilar-Hernández
authors.forename: Tomas
authors.initials: T
authors.lastname: Monfil
authors.forename: Miguel
authors.initials: M
authors.lastname: Cervantes
authors.forename: Gabriela
authors.initials: G
authors.lastname: Moralí
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism*; D053938:DNA Fragmentation / Q000187:drug effects*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011374:Progesterone / Q000494:pharmacology* / Q000627:therapeutic use; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D018696:Neuroprotective Agents; D011374:Progesterone; D053148:Caspase 3
keywords: Caspase-3; DNA fragmentation; Global cerebral ischemia; Neuroprotection; Progesterone